The ends of the chromosomes, the telomeres, are repetitive DNA sequences that shorten every time a cell divides during the process of duplicating its genome. Once the telomeres become very short the cell stops dividing. Thus, telomeres work like a cellular clock that keeps an eye on the number of cell divisions.
And once the cell's time is over it can no longer divide. Circumventing this control mechanism is crucial for tumor cells in order to proliferate without limits. In the majority of tumors this is accomplished by reactivating telomerase, an enzyme that normally extends the telomeres only in embryonic cells, and thus resets the cellular clock during development. However, a 10-15% fraction of tumors keeps on dividing without telomerase by making use of what is called the ALT-mechanism for "Alternative Lengthening of Telomeres". The hallmark of ALT cancer cells is a special type of complexes of promyelocytic leukemia (PML) protein at the telomeres that are termed ALT-associated PML nuclear bodies or APBs.
ALT-tumors can be identified by the presence of APBs on fluorescence microscopy images since normal cells do not have these structures. However, the function of APBs has remained mysterious. In a recent study, Inn Chung and Karsten Rippe from the German Cancer Research Center together with Heinrich Leonhard from the LMU in Munich applied a novel approach to study APBs. They succeeded in artificially making APBs in living cells by tethering PML and other APB proteins to the telomeres. In this manner they could not only trace the assembly of APBs but were able to investigate what happens after APB formation. They could show that the de novo formed APBs induced the extension of the telomere repeat sequence by a DNA repair synthesis mechanism. This demonstrates for the first time that APBs have an important function for the alternative telomere lengthening mechanism, and suggests that disrupting APBs would stop proliferation of ALT-positive tumor cells once their telomeres become too short. This makes APBs a promising new target of cancer cells, in which the ALT mechanism is active.
Publication: Chung, I., Leonhardt, H. & Rippe, K. (2011). De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation. J. Cell Sci., doi: 10.1242/jcs.084681.
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), employing over 2,500 staff members, is the largest biomedical research institute in Germany. More than 1,000 scientists are working to investigate the mechanisms of cancer development, identify cancer risk factors and develop new strategies for better cancer prevention, more precise diagnosis and effective treatment of cancer patients. In addition, the staff of the Cancer Information Service (KID) provides information about this widespread disease for patients, their families, and the general public. DKFZ is funded by the German Federal Ministry of Education and Research (90%) and the State of Baden-Wuerttemberg (10%) and is a member of the Helmholtz Association of National Research Centers.
Dr. Sibylle Kohlstaedt | EurekAlert!
New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences
The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences